Maintenance of the transformed phenotype in DNA and RNA tumor virus transformed cells and in cultured human tumors will be investigated with the goal of identifying cellular or viral factors responsible for driving cells through the cell cycle. Cells transformed by SV40 ts A mutants exhibit temperature sensitivity for uncontrolled DNA synthesis. Cells transformed by small t-antigen deletion mutants exhibit uncontrolled DNA synthesis. Therefore, the large T-antigen gene and not the small t-antigen is responsible for driving cells through the cell cycle. In contrast to DNA virus transformants, RNA virus transformants are arrested in G1 by cytochalasin B, caffeine and low serum. The driving force for DNA synthesis is suppressed in somatic cell hybrids and hybrids of normal X transformed cells. Suppression factors appear to be coded in the nucleus but persist in the cytoplasm. The second part of the program proposes to investigate the role of papovavirus defective interfering particles (DIs) in initiation of transformation and their role in viral persistence and latency. Defective interfering genomes (DIs) of SV40 play a positive role in transformation of some permissive cells, but in other permissive cells they are protective and generate latent infections. But in either case, they prevent cell killing by wt virus and help to establish persistent infections. A new strain of SV40 was isolated which contains the genome split into two molecules. One contains all of the early coding sequences and the other the late coding sequences. However, each of the genomes of EL SV40 is a defective and contains reiterations of the viral origin and viral terminus. Papovavirus defectives are amplified during low-multiplicity infections of a variety of neural and non-neural cells.